Solid state forms of tapentadol salts

Abstract

Provided herein are novel solid state forms of tapentadol salts, process for their preparation, pharmaceutical compositions, and method of treating thereof. The tapentadol salts include an L-(−)-camphorsulfonate salt, a dibenzoyl-(L)-tartrate salt, a dibenzoyl-(D)-tartrate salt, a malate salt, a maleate salt, or a salicylate salt.

We claim: 
     
       1. A solid state form of a salt of 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl] phenol (tapentadol salt), wherein the salt of tapentadol is a maleate salt and is characterized by one or more of the following properties
 i) a powder X-ray diffraction pattern in accordance with  FIG. 9 ; 
 ii) a powder X-ray diffraction pattern having peaks at 15.31, 16.08, 21.08, 27.95, 28.53 and 29.51±0.2 degrees 2-theta; and 
 iii) a powder X-ray diffraction pattern having peaks at 19.13, 20.44, 22.90, 24.76, 30.66, 31.06, 31.81, 33.80, 34.84, 35.29, 38.31, 40.26, 40.68 and 43.16±0.2 degrees 2-theta. 
 
     
     
       2. The solid state form of tapentadol salt of  claim 1 , further characterized by
 a differential scanning calorimetric (DSC) thermogram substantially in accordance with  FIG. 10 . 
 
     
     
       3. A pharmaceutical composition comprising the solid state form of a tapentadol maleate salt of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
       4. The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition is a solid dosage form, an oral suspension, a liquid, a powder, an elixir, an aerosol, a syrup, or an injectable solution. 
     
     
       5. The pharmaceutical composition of  claim 3 , wherein the pharmaceutical composition is a solid dosage form. 
     
     
       6. The pharmaceutical composition of  claim 3 , wherein the solid state form of tapentadol salt has a D 90  particle size of less than or equal to about 500 microns. 
     
     
       7. The pharmaceutical composition of  claim 3 , wherein the D 90  particle size is about 1 micron to about 300 microns, or about 10 microns to about 150 microns. 
     
     
       8. A method for treating a patient suffering from severe acute pain; comprising administering a solid state form of tapentadol salt, or a pharmaceutical composition that comprises the solid state form of tapentadol salt along with a pharmaceutically acceptable excipient, wherein the salt of tapentadol is a maleate salt in accordance with  claim 1 . 
     
     
       9. A process for the preparation of solid state form of tapentadol salt of  claim 1 , comprising:
 a) providing a first solution or a suspension of tapentadol free base in a solvent, wherein the solvent is selected from the group consisting of water, methanol, ethanol, isopropyl alcohol, acetonitrile, and mixtures thereof; 
 b) combining the first solution or suspension with an acid to produce a second solution or suspension containing a tapentadol acid addition salt, wherein the acid is maleic acid; and 
 c) isolating and/or recovering the solid state form of the tapentadol salt from the second solution or suspension obtained in step-(b). 
 
     
     
       10. The process of  claim 9 , wherein the first solution in step-(a) is prepared by dissolving tapentadol free base in the solvent at a temperature of below about boiling temperature of the solvent used; wherein the suspension in step-(a) is provided by suspending tapentadol free base in the solvent while stirring at a temperature of about 0° C. to the reflux temperature of the solvent used; wherein the first solution or suspension obtained in step-(a) is optionally stirred at a temperature of about 25° C. to the reflux temperature of the solvent for about 20 minutes to about 5 hours; wherein the combining in step-(b) is accomplished by adding the first solution or suspension to the acid or by adding the acid to the first solution or suspension, at a temperature of below about 50° C.; wherein the reaction mass obtained after completion of the addition process in step-(b) is stirred at a temperature of about 50° C. to the reflux temperature of the solvent for at least 10 minutes to produce a second solution or suspension; wherein the second solution obtained in step-(b) is optionally subjected to carbon treatment or silica gel treatment; wherein the isolation of pure solid state form of tapentadol salt in step-(c) is carried out by crystallization, substantial removal of the solvent from the solution or suspension, or a combination thereof; wherein the recovering in step-(c) is carried out by filtration, filtration under vacuum, decantation, centrifugation, filtration employing a filtration media of a silica gel or celite, or a combination thereof; and wherein the substantially pure solid state form of tapentadol salt obtained is further dried under vacuum or at atmospheric pressure, at a temperature of about 35° C. to about 80° C. 
     
     
       11. The process of  claim 10 , wherein the tapentadol free base is dissolved in the solvent at a temperature of about 20° C. to about 110° C.; wherein the suspension is stirred at a temperature of about 20° C. to about 110° C. for at least 30 minutes; wherein the addition in step-(b) is carried out at a temperature of about 15° C. to about 35° C.; wherein the reaction mass obtained after completion of the addition process in step-(b) is stirred at a temperature of about 55° C. to about 100° C. for about 20 minutes to about 10 hours; wherein the crystallization is initiated by cooling, seeding, partial removal of the solvent from the solution, by adding an anti-solvent to the solution, or a combination thereof; and wherein the removal of solvent is accomplished by substantially complete evaporation of the solvent, concentrating the solution or distillation of solvent under inert atmosphere, spray drying, vacuum drying, agitated thin-film (ATFD) drying, or a combination thereof. 
     
     
       12. The process of  claim 11 , wherein the crystallization is carried out by cooling the solution while stirring at a temperature of about 0° C. to about 30° C. for about 10 minutes to about 20 hours; and wherein the anti-solvent is selected from the group consisting of n-pentane, n-hexane, n-heptane, cyclohexane, toluene, xylene, tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, monoglyme, diglyme, and mixtures thereof.